1. Ozone/Oxygen-injections in cases of disc hernia - Die Ozon/Sauerstoff-Injektion beim Bandscheibenvorfall Thomas Lehnert, T.J. Vogl Department of Diagnostic and Interventional Radiology Johann Wolfgang Goethe University Clinic Frankfurt/Main, Germany

2. Indications Combined intradiscal and periganglionic injection of medical ozone Combined intradiscal an periganglionic injection of medical ozone is reserved for patients failing to respond to conservative treatment.

3. Indications Combined intradiscal and periganglionic injection of medical ozone Neurological Examination CT / MR Examination O 2 /O 3 - Injection Precondition to O 2 /O 3 -injectionAftercare of O 2 /O 3 -injection CT / MR Examination Neurological Examination

4. Indications Combined intradiscal and periganglionic injection of medical ozone 256 x 100 512 x 60 512 x 50 512 x 60 512 x 50 Image matrix 15 17 109 15 109 49 TE (in ms)‏ 19 15 18 Slices (per slab)‏ 600 550 3600 500 4000 4560 TR (in ms)‏ 4 4 4 4 4 4 S-thickness (in mm)‏ 10090° t1_se_sag_reph_fs 10090° t1_se_sag 100160° t2_tirm_sag 100 64 100 FoV phase (in mm)‏ Siemens Magnetom Symphony / Siemens Magnetom Sonata 90° 180° Flip angle t2_tse_tvs t1_se_tvs_fs t2_tse_sag Sequence

5. Indications Combined intradiscal and periganglionic injection of medical ozone - major neurologic deficits - referred allergy to proposed drugs - facet syndrom - sacroileitis - bone lesions (infective, inflammatory, neoplastic)‏ - previous spine surgery - lumbar disc herniation on CT/MR images - monoradicular pain - herniation site congruous with the neurologic level Inclusion O 2 /O 3 -injection Exclusion O 2 /O 3 -injection

6. Procedure Combined intradiscal and periganglionic injection of medical ozone Medical oxygen Clinico Biozomat 11T (Bad Hersfeld, Germany)‏ Siemens Somatom Plus 4 (Erlangen, Germany)‏

7. Procedure Combined intradiscal and periganglionic injection of medical ozone 120 Tube voltage (in kV)‏ 200 Tube current (in mAs)‏ 4 TF/R (in mm)‏ 1.5 / 0.7 Thickness/Increment (in mm)‏ 4 x 1 non enhanced Siemens Somatom Plus 4 CollimationPhase ~ 45 BiopsyComb DLP (mGy.cm)‏ ~ 300 Helical scan

8. Intervention planning Combined intradiscal and periganglionic injection of medical ozone

9. Intervention planning Combined intradiscal and periganglionic injection of medical ozone

10. Procedure Combined intradiscal and periganglionic injection of medical ozone 1 mL corticosteroid (Celestan ® depot)‏ 2 mL anesthetic (Carbostesin ® 0.25%)‏ 7 mL O 2 /O 3 (ratio 97:3)‏ 3 mL O 2 /O 3 (ratio 97:3)‏

11. Procedure Results

12. Biochemical mechanism Combined intradiscal and periganglionic injection of medical ozone The herniation can impinge on the venous and arterial flow and cause phlebostasis and arteriostenosis. These conditions can lead to a serious hypoxemia and pain. By applying the oxygen to herniation area, both a direct and indirect hyperoxygenation occurs, which reduces the pain. Reduction of anoxia Ozone has an effect on the disc inflammation by altering the breakdown of arachidonic acid to inflammatory prostaglandins. Therefore, by reducing the inflammatory components there is a corresponding reduction of pain. Reduction of inflammatory components Ozone has a direct effect on the proteoglycans in the nucleus pulposus. The water binding capacity of proteoglycans is the main force that holds water to the nucleus pulposus. Destruction of the proteoglycans reduces the hold water and therefore diminishing the size of herniation. Reduction of hold water in nucleus pulposus

13. Purpose of study Combined intradiscal and periganglionic injection of medical ozone To evaluate the therapeutic benefit and morphologic changes in herniated lumbar disk after CT-guided intradiscal and periganglionic ozone-oxygen injection combined with a periganglionic administration of steroids and anesthetic.

14. Patients group Combined intradiscal and periganglionic injection of medical ozone n=39 (42.4%)‏ n=18 (19.5%)‏n=49 (53.3%)‏83 n=10 (10.9%)‏n=43 (46.7%)‏24 n=2 (2.2%)‏n=9254.1 n=23 (25.0%)‏ L5/S1 L4/L5 L3/L4 L2/L3 L1/L2 Localisation herniated disk male female overall Gender max. min. ∅ Age in years

15. Time schedule Combined intradiscal and periganglionic injection of medical ozone + + + + + + Evaluation Changes in radiculopathy + + - - - + Evaluation Changes in disk volume - - - - + - CT + + - - - + MRI 7 days 6 months 3 months 1 month injection before

16. Results Combined intradiscal and periganglionic injection of medical ozone - 0.8 - 1-3 - 0.6 - 1.5 - 1.9 - 1.4 - 0.9 - 1.5 - 1.2 - 4.2 - 0.4 - 1.1 - 0.7 - 1.1 - 1.0 - 0.9 - 0.6 - 0.1 - 0.9 - 2.5 1.41.82.2 Traveling 1.52.43.4 Standing 1.41.72.3 Motility 1.31.62.5 Self supply 1.6 1.2 1.5 2.1 2.4 Evaluation 6 months after therapy 1.8 1.1 1.6 2.0 3.5 4.1 Evaluation 1 week after therapy 2.9 1.8 2.7 2.9 3.6 6.6 Evaluation before therapy Sitting Social life Sex life Sleeping Physical constitution Pain intensity

17. Results 6 months after O 2 /O 3 -injection DescriptionOutcome n=2 (2.2%)‏ n=17 (18.5%)‏ n=27 (29.3%)‏ n=46 (50.0%)‏ Patients max.min.mean + 1.7% - 0.8% - 3.6% - 6.0% + 3.0% - 6.4% - 16.2% - 19.3% Disk volume reduction + 2.4 % - 4.1 % - 8.3 % - 14.0 % - No improvement - Worsening of clinical situation - Insufficient improvement of symptoms - Periodic administration of drugs - Limitation of physical activities - Occasional episodes of low back pain or sciatica - No limitations of occupational activities - Disappearance of symptoms - Complete recovery in working - Complete recovery in sports poor surgery good excellent Modified MacNab method

18. Results / Complications Combined intradiscal and periganglionic injection of medical ozone - - n=18 (19.6%)‏ n=58 (63.0%)‏ 1 month - - - - injection 6 months3 months7 days - - n=21 (22.9%)‏ n=49 (53.3%)‏ - - n=19 (20.7%)‏ n=51 (55.4%)‏ after O 2 /O 3 -injection - 1 n=13 (14.1%)‏ - - - n=88 (95.7%)‏ n=82 (89.1%)‏ before Severe complications Allergic reactions Analgetics Physical therapy

19. Treatment success 6 months after O 2 /O 3 -injection before O 2 /O 3 -injection

20. Treatment success 6 months after O 2 /O 3 -injection before O 2 /O 3 -injection

21. Literature review Combined intradiscal and periganglionic injection of medical ozone n=179.3%n=922006 Lehnert T et al. n=0 complications after therapy 74.0% 90.0% 80.0% 78.3% success 6 months after therapy n=82 n=30 n=1750 n=300 patients 2007 2005 2004 2003 year Buric J et al. Gallucci M et al. Muto M et al. Andreula CF et al.

22. Complication Combined intradiscal and periganglionic injection of medical ozone Lo Giudice G, Valdi F, Gismondi M, Prosdocimo G, de Belvis V Acute bilateral vitreo-retinal hemorrhages following oxygen-ozone therapy for lumbar disk herniation. Am J Ophthalmol. 2004 Jul;138(1):175-7. „…the real mechanism of action producing intraocular hemorrhages after intradiscal infiltration of O 2 O 3 is unclear.“ „…an abrupt, transient spike in cerebrospinal fluid pressure after disk infiltration was responsible for the retinal hemorrhages. Although an accidental injection delivered directly into epidural space cannot be excluded, we also suggest that an increased intradiscal pressure with an overload and microrupture of the disk after the injection could have caused a quick spread of the mixture into epidural space proportional to the speed and volume of the infiltration. An increase in cerebrospinal fluid pressure after the injection was thus transmitted directly through the optic nerve sheaths to the retinal venous circulation, thus causing distension and rupture of peripapillary and retinal capillaries.“

23. Complication Combined intradiscal and periganglionic injection of medical ozone Ginanneschi F, Cervelli C, Milani P, Rossi A Ventral and dorsal root injury after oxygen-ozone therapy for lumbar disk herniation. Surg Neurol. 2006 Dec;66(6):619-20. „The real mechanism underlining this double injury is not clear.“ „The hypothesis of a direct toxic effect of ozone is unremarkable.“ „Concerning the pathophysiology of the lesion, it could be hypothesized that an abrupt and transient increase of the CFP causes focal damage by means of mechanical mechanism, in the form of direct root trauma. The possibility of direct damage by needle introduction may be clinically excluded because the subject did not complain of electric shock sensation after needle introduction. In conclusion, we suggest that root injury after O 2 O 3 therapy for lumbar disk herniation should be considered an uncommon but significant complication.“

24. Complication Combined intradiscal and periganglionic injection of medical ozone Gazzeri R, Galarza M, Neroni M, Esposito S, Alfieri A Fulminating septicemia secondary to oxygen-ozone therapy for lumbar disc herniation: case report. Spine. 2007 Feb;32(3):E121-3. „Autopsy confirmed an acute bilateral lobar pneumonia and paraspinal muscle abscess, with positive results for E. coli. Spinal canal content was relatively intact.“ „…most likely pathophysiological mechanism in our case was direct inoculation of the bacteria during the procedure. Wound or systemic infections in ozone therapy are mostly related to a lack of sterility during the administration of therapy.“ „…secondary pneumonia might have originated from the hematological spread of bacteria from the paraspinal abscess.“ „…prophylactic antibiotic therapy should always be given to the patient.“

25. Conclusion Combined intradiscal and periganglionic injection of medical ozone The combined intradiscal and periganglionic injection of medical ozone and periganglionic administration of steroids and anesthetic offers a treatment option for lumbar disk herniation that has failed to respond to conservative management, before recourse to surgery or when surgery is not possible. Its ease of execution permits the successful outpatient treatment of lumbar sciatic pain.

26. Conclusion Conservative management 13 months after conservative management before treatment